Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia

Karin A. Fox, Monica Longo, Esther Tamayo, Talar Kechichian, Egle Bytautiene, Gary Hankins, George Saade, Maged Costantine

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

OBJECTIVE: We sought to investigate the mechanisms of action by which pravastatin improves vascular reactivity in a mouse model of preeclampsia induced by overexpression of soluble Fms-like tyrosine kinase-1 (sFlt)-1. STUDY DESIGN: Pregnant CD-1 mice were randomly allocated to tail vein injection with adenovirus carrying sFlt-1 or murine immunoglobulin G2 Fc (control), and thereafter to receive pravastatin (5 mg/kg/d) or water. Mice were sacrificed at gestational day 18. Protein expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor receptor-1, and hemeoxygenase-1 were assayed by Western blot in aorta, liver, and kidneys. Serum total cholesterol concentrations were measured. RESULTS: Pravastatin up-regulated eNOS expression in the aorta of sFlt-1 mice by nearly 2-fold (P=.005) to levels similar to control mice. Total cholesterol levels, vascular endothelial growth factor receptor-1, and hemeoxygenase-1 protein expression were similar across groups. CONCLUSION: Pravastatin prevents vascular dysfunction in part by upregulation of eNOS in the vasculature. Our data support a role for statins in preeclampsia prevention.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume205
Issue number4
DOIs
StatePublished - Oct 2011

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Vascular Endothelial Growth Factor Receptor-1
Pravastatin
Pre-Eclampsia
Blood Vessels
Nitric Oxide Synthase Type III
Heme Oxygenase-1
Aorta
Cholesterol
Immunoglobulin Fc Fragments
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Adenoviridae
Tail
Veins
Proteins
Up-Regulation
Western Blotting
Kidney
Injections
Water
Liver

Keywords

  • CD-1 mouse
  • Endothelial nitric oxide synthase
  • Pravastatin
  • Preeclampsia
  • Soluble Fms-like tyrosine kinase-1

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia. / Fox, Karin A.; Longo, Monica; Tamayo, Esther; Kechichian, Talar; Bytautiene, Egle; Hankins, Gary; Saade, George; Costantine, Maged.

In: American Journal of Obstetrics and Gynecology, Vol. 205, No. 4, 10.2011.

Research output: Contribution to journalArticle

Fox, Karin A. ; Longo, Monica ; Tamayo, Esther ; Kechichian, Talar ; Bytautiene, Egle ; Hankins, Gary ; Saade, George ; Costantine, Maged. / Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia. In: American Journal of Obstetrics and Gynecology. 2011 ; Vol. 205, No. 4.
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